Contributions to the studies of asparaginyl peptide ligases and to the design of inhibitors targeting bacterial tRNA methyltransferases

Abstract

Enzymes constitute very important macromolecular catalysts with a wide range of biological activities. During my thesis work, I have studied two important enzymes using a combination of biochemical and structural biology tools. So my thesis is naturally broken down into two main parts, each part being dedicated to the study of one type of enzyme. The first enzyme is a peptide ligase that belongs to the ligase categories. It is an asparaginyl peptide ligase, which is a very powerful precision conjugation tool with many applications in biochemistry and biotechnology. It recognizes and cleaves the peptide bond that follows an Asx (Asn/Asp) residues at P1 position. The second enzyme is a tRNA methyltransferase, TrmD from Pseudomonas aeruginosa, an attractive drug target to overcome bacterial drug resistance. For each enzyme, I have performed a thorough functional and structural characterization and the results I am presenting here have attractive implications in biotechnology and for drug design.